We propose to select two classes of mutants in teratocarcinoma cells: mutations in purine metabolism and in cell surface characteristics (lectin resistance). We will ask how these mutations affect the ability of the cells to differentiate in vitro, in vivo in solid tumors, and in vivo in mice. In addition we propose to investigate methods for facilitating the production of mutant mice from mutant teratocarcinoma cells. We will karyotype existing teratocarcinoma cells, and, using the most chromosomally normal lines, will attempt to replace the inner cell masses of blastocysts completely with teratocarcinoma cells. Failing that, we will produce chimeras whose composition is biased in favor of the teratocarcinoma component, by creating inner cell masses containing teratocarcinoma cells and one or a minimal number of normal inner cell mass cells.